{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T15:10:06Z","timestamp":1790781006186,"version":"4.1.0"},"reference-count":105,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2017,8,7]],"date-time":"2017-08-07T00:00:00Z","timestamp":1502064000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"Natural Science Foundation of China","doi-asserted-by":"publisher","award":["U1305212"],"award-info":[{"award-number":["U1305212"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"publisher","award":["2016YFD0500205"],"award-info":[{"award-number":["2016YFD0500205"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]},{"name":"National Key National Basic Research Program (973) of China","award":["2015CB910502"],"award-info":[{"award-number":["2015CB910502"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Influenza A virus (IAV), a highly infectious respiratory pathogen, has continued to be a significant threat to global public health. To complete their life cycle, influenza viruses have evolved multiple strategies to interact with a host. A large number of studies have revealed that the evolution of influenza A virus is mainly mediated through the mutation of the virus itself and the re-assortment of viral genomes derived from various strains. The evolution of influenza A virus through these mechanisms causes worldwide annual epidemics and occasional pandemics. Importantly, influenza A virus can evolve from an animal infected pathogen to a human infected pathogen. The highly pathogenic influenza virus has resulted in stupendous economic losses due to its morbidity and mortality both in human and animals. Influenza viruses fall into a category of viruses that can cause zoonotic infection with stable adaptation to human, leading to sustained horizontal transmission. The rapid mutations of influenza A virus result in the loss of vaccine optimal efficacy, and challenge the complete eradication of the virus. In this review, we highlight the current understanding of influenza A virus evolution caused by the mutation and re-assortment of viral genomes. In addition, we discuss the specific mechanisms by which the virus evolves.<\/jats:p>","DOI":"10.3390\/ijms18081650","type":"journal-article","created":{"date-parts":[[2017,8,8]],"date-time":"2017-08-08T10:28:08Z","timestamp":1502188088000},"page":"1650","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":377,"title":["Evolution of Influenza A Virus by Mutation and Re-Assortment"],"prefix":"10.3390","volume":"18","author":[{"given":"Wenhan","family":"Shao","sequence":"first","affiliation":[{"name":"Key Laboratory of Fujian-Taiwan Animal Pathogen Biology, College of Animal Sciences, Fujian Agriculture and Forestry University, Fuzhou 350002, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinxin","family":"Li","sequence":"additional","affiliation":[{"name":"Key Laboratory of Fujian-Taiwan Animal Pathogen Biology, College of Animal Sciences, Fujian Agriculture and Forestry University, Fuzhou 350002, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6501-0662","authenticated-orcid":false,"given":"Mohsan","family":"Goraya","sequence":"additional","affiliation":[{"name":"Key Laboratory of Fujian-Taiwan Animal Pathogen Biology, College of Animal Sciences, Fujian Agriculture and Forestry University, Fuzhou 350002, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Song","family":"Wang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Fujian-Taiwan Animal Pathogen Biology, College of Animal Sciences, Fujian Agriculture and Forestry University, Fuzhou 350002, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ji-Long","family":"Chen","sequence":"additional","affiliation":[{"name":"Key Laboratory of Fujian-Taiwan Animal Pathogen Biology, College of Animal Sciences, Fujian Agriculture and Forestry University, Fuzhou 350002, China"},{"name":"CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2017,8,7]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1017\/S1466252310000071","article-title":"Perspectives on influenza evolution and the role of research","volume":"11","author":"Forrest","year":"2010","journal-title":"Anim. Health Res. Rev."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1229","DOI":"10.1086\/502973","article-title":"Clinical features of influenza C virus infection in children","volume":"193","author":"Matsuzaki","year":"2006","journal-title":"J. Infect. Dis."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1861","DOI":"10.1098\/rstb.2001.0999","article-title":"The evolution of human influenza viruses","volume":"356","author":"Hay","year":"2001","journal-title":"Philos. Trans. R. Soc. Lond. B. Biol. Sci."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"252","DOI":"10.1016\/j.jinf.2011.04.013","article-title":"A definition for influenza pandemics based on historical records","volume":"63","author":"Potter","year":"2011","journal-title":"J. Infect."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"188","DOI":"10.1016\/S0753-3322(00)89025-3","article-title":"The epidemiology and history of influenza","volume":"54","author":"Kuszewski","year":"2000","journal-title":"Biomed. Pharmacother."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"904","DOI":"10.1038\/nature03063","article-title":"Transmissibility of 1918 pandemic influenza","volume":"432","author":"Mills","year":"2004","journal-title":"Nature"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"572","DOI":"10.1046\/j.1365-2672.2001.01492.x","article-title":"A history of influenza","volume":"91","author":"Potter","year":"2001","journal-title":"J. Appl. Microbiol."},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Biggerstaff, M., Cauchemez, S., Reed, C., Gambhir, M., and Finelli, L. (2014). Estimates of the reproduction number for seasonal, pandemic, and zoonotic influenza: A systematic review of the literature. BMC Infect. Dis., 14.","DOI":"10.1186\/1471-2334-14-480"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"43566","DOI":"10.1038\/srep43566","article-title":"Continual antigenic diversification in China leads to global antigenic complexity of avian influenza H5N1 viruses","volume":"7","author":"Peng","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"822","DOI":"10.1016\/S1473-3099(17)30323-7","article-title":"Epidemiology of avian influenza A H7N9 virus in human beings across five epidemics in mainland China, 2013\u201317: An epidemiological study of laboratory-confirmed case series","volume":"17","author":"Wang","year":"2017","journal-title":"Lancet. Infect. Dis."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1126\/science.1222213","article-title":"An overlapping protein-coding region in influenza A virus segment 3 modulates the host response","volume":"337","author":"Jagger","year":"2012","journal-title":"Science"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"407","DOI":"10.1146\/annurev.med.51.1.407","article-title":"Global epidemiology of influenza: Past and present","volume":"51","author":"Cox","year":"2000","journal-title":"Annu. Rev. Med."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"475","DOI":"10.1016\/0042-6822(91)90588-3","article-title":"Comparison of complete amino acid sequences among 13 serotypes of Hemagglutinins and receptor-binding properties of influenza A viruses indirect immunofluorescence","volume":"182","author":"Aoyama","year":"1991","journal-title":"Virology"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"590","DOI":"10.1038\/nrmicro2613","article-title":"Influenza A viruses: New research developments","volume":"9","author":"Medina","year":"2011","journal-title":"Nat. Rev. Microbiol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"17736","DOI":"10.1073\/pnas.0807142105","article-title":"Structure of influenza Hemagglutinin in complex with an inhibitor of membrane fusion","volume":"105","author":"Russell","year":"2008","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1078","DOI":"10.1371\/journal.ppat.1003657","article-title":"New world bats harbor diverse influenza A viruses","volume":"9","author":"Tong","year":"2013","journal-title":"PLoS Path."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1733","DOI":"10.1016\/S0140-6736(03)14854-4","article-title":"Influenza","volume":"362","author":"Nicholson","year":"2003","journal-title":"Lancet."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"823","DOI":"10.1002\/embj.201387442","article-title":"Role of receptor binding specificity in influenza A virus transmission and pathogenesis","volume":"33","author":"Fouchier","year":"2014","journal-title":"EMBO J."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"409","DOI":"10.1016\/S0092-8674(00)81771-7","article-title":"Structure of the hemagglutinin precursor cleavage site, a determinant of influenza pathogenicity and the origin of the labile conformation","volume":"95","author":"Chen","year":"1998","journal-title":"Cell"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"196","DOI":"10.1016\/S0753-3322(00)89026-5","article-title":"Influenza virus genetics","volume":"54","author":"Brown","year":"2000","journal-title":"Biomed. Pharmacother."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1016\/j.virusres.2004.02.034","article-title":"Molecular mechanisms of influenza virus resistance to neuraminidase inhibitors","volume":"103","author":"Gubareva","year":"2004","journal-title":"Virus. Res."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1099","DOI":"10.1128\/jvi.69.2.1099-1106.1995","article-title":"Influenza type A virus neuraminidase does not play a role in viral entry, replication, assembly, or budding","volume":"69","author":"Liu","year":"1995","journal-title":"J. Virol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1287","DOI":"10.1016\/j.micinf.2005.12.008","article-title":"Roles of neuraminidase in the initial stage of influenza virus infection","volume":"8","author":"Ohuchi","year":"2006","journal-title":"Microbes. Infect."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1266","DOI":"10.1038\/nsmb.1909","article-title":"The 2009 pandemic H1N1 neuraminidase N1 lacks the 150-cavity in its active site","volume":"17","author":"Li","year":"2010","journal-title":"Nat. Struct. Mol. Biol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"428","DOI":"10.1007\/s11427-009-0062-z","article-title":"Interspecies transmission and host restriction of avian H5N1 influenza virus","volume":"52","author":"Liu","year":"2009","journal-title":"Sci. China C Life Sci."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"975","DOI":"10.1016\/j.cmi.2016.07.007","article-title":"Functional balance between neuraminidase and haemagglutinin in influenza viruses","volume":"22","author":"Gaymard","year":"2016","journal-title":"Clin. Microbiol. Infect."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1016\/j.virusres.2006.09.013","article-title":"Nuclear traffic of influenza virus proteins and ribonucleoprotein complexes","volume":"124","author":"Boulo","year":"2007","journal-title":"Virus. Res."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"391","DOI":"10.1016\/0092-8674(81)90208-7","article-title":"Influenza virus, an RNA virus, synthesizes its messenger RNA in the nucleus of infected cells","volume":"26","author":"Herz","year":"1981","journal-title":"Cell"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"2424","DOI":"10.3390\/v5102424","article-title":"Transport of the Influenza virus genome from nucleus to nucleus","volume":"5","author":"Hutchinson","year":"2013","journal-title":"Viruses"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1002\/wrna.1321","article-title":"lncRNAs regulate the innate immune response to viral infection","volume":"7","author":"Ouyang","year":"2016","journal-title":"Wiley Interdiscip. Rev. RNA"},{"key":"ref_31","first-page":"10321","article-title":"Robust expression of vault RNAs induced by influenza A virus plays a critical role in suppression of PKR-mediated innate immunity","volume":"43","author":"Li","year":"2015","journal-title":"Nucleic Acids Res."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"315","DOI":"10.1038\/nri3665","article-title":"Innate immunity to influenza virus infection","volume":"14","author":"Iwasaki","year":"2014","journal-title":"Nat. Rev. Immunol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"513","DOI":"10.1146\/annurev-immunol-032713-120231","article-title":"Interferon-stimulated genes: A complex web of host defenses","volume":"32","author":"Schneider","year":"2014","journal-title":"Annu. Rev. Immunol."},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Wei, H., Wang, S., Chen, Q., Chen, Y., Chi, X., Zhang, L., Huang, S., Gao, G.F., and Chen, J.L. (2014). Suppression of interferon lambda signaling by SOCS-1 results in their excessive production during influenza virus infection. PLoS Pathog., 10.","DOI":"10.1371\/journal.ppat.1003845"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"8375","DOI":"10.1128\/JVI.00126-14","article-title":"Influenza A virus-induced degradation of eukaryotic translation initiation factor 4B contributes to viral replication by suppressing IFITM3 protein expression","volume":"88","author":"Wang","year":"2014","journal-title":"J. Virol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"712","DOI":"10.1007\/s13238-015-0191-z","article-title":"Induction of innate immunity and its perturbation by influenza viruses","volume":"6","author":"Goraya","year":"2015","journal-title":"Protein Cell"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"5180","DOI":"10.4049\/jimmunol.0804198","article-title":"Essential impact of NF-kappaB signaling on the H5N1 influenza A virus-induced transcriptome","volume":"183","author":"Schmolke","year":"2009","journal-title":"J. Immunol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"592","DOI":"10.1093\/infdis\/jir352","article-title":"Critical role of serpinB1 in regulating inflammatory responses in pulmonary influenza infection","volume":"204","author":"Gong","year":"2011","journal-title":"J. Infect. Dis."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1270","DOI":"10.1126\/science.1069132","article-title":"RNA-dependent RNA polymerases, viruses, and RNA silencing","volume":"296","author":"Ahlquist","year":"2002","journal-title":"Science"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"2336","DOI":"10.1093\/molbev\/msl102","article-title":"Avian influenza virus exhibits rapid evolutionary dynamics","volume":"23","author":"Chen","year":"2006","journal-title":"Mol. Biol. Evol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1463","DOI":"10.1126\/science.1236787","article-title":"An airborne transmissible avian influenza H5 hemagglutinin seen at the atomic level","volume":"340","author":"Zhang","year":"2013","journal-title":"Science"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"503","DOI":"10.1006\/viro.1993.1155","article-title":"Genetic reassortment between avian and human influenza A viruses in Italian pigs","volume":"193","author":"Castrucci","year":"1993","journal-title":"Virology"},{"key":"ref_43","first-page":"158","article-title":"The pig as a mixing vessel for influenza viruses: Human and veterinary implications","volume":"3","author":"Ma","year":"2008","journal-title":"J. Mol. Genet. Med."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"440","DOI":"10.1016\/j.chom.2010.05.009","article-title":"Influenza virus evolution, host adaptation, and pandemic formation","volume":"7","author":"Taubenberger","year":"2010","journal-title":"Cell Host Microbe"},{"key":"ref_45","first-page":"152","article-title":"Evolution and ecology of influenza A viruses","volume":"56","author":"Webster","year":"1992","journal-title":"Curr. Top Microbiol. Immunol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1750","DOI":"10.1128\/JVI.06203-11","article-title":"Reassortment and mutation of the avian influenza virus polymerase PA Subunit overcome species barriers","volume":"86","author":"Mehle","year":"2012","journal-title":"J. Virol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"6852","DOI":"10.1016\/j.vaccine.2007.07.027","article-title":"Influenza vaccine: The challenge of antigenic drift","volume":"25","author":"Carrat","year":"2007","journal-title":"Vaccine"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"3058","DOI":"10.1038\/srep03058","article-title":"Adaptation of novel H7N9 influenza A virus to human receptors","volume":"3","author":"Dortmans","year":"2013","journal-title":"Sci. Rep."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"496","DOI":"10.1038\/nature12372","article-title":"Receptor binding by an H7N9 influenza virus from humans","volume":"499","author":"Xiong","year":"2013","journal-title":"Nature"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"9911","DOI":"10.1128\/JVI.01175-13","article-title":"Increased acid stability of the Hemagglutinin protein enhances H5N1 influenza virus growth in the upper respiratory tract but is insufficient for transmission in ferrets","volume":"87","author":"Zaraket","year":"2013","journal-title":"J. Virol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"3794","DOI":"10.1128\/JVI.03052-15","article-title":"Amino acid substitutions that affect receptor binding and stability of the Hemagglutinin of influenza A\/H7N9 virus","volume":"90","author":"Schrauwen","year":"2016","journal-title":"J. Virol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"917","DOI":"10.1007\/s10822-016-9981-5","article-title":"Role of R292K mutation in influenza H7N9 neuraminidase toward oseltamivir susceptibility: MD and MM\/PB(GB)SA study","volume":"30","author":"Phanich","year":"2016","journal-title":"J. Comput. Aided Mol. Des."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"33334","DOI":"10.1038\/srep33334","article-title":"Long-term adaptation of the influenza A virus by escaping cytotoxic T-cell recognition","volume":"6","author":"Woolthuis","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"987","DOI":"10.1099\/vir.0.041228-0","article-title":"Role of Itk signalling in the interaction between influenza A virus and T-cells","volume":"93","author":"Fan","year":"2012","journal-title":"J. Gen. Virol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"6363","DOI":"10.1016\/j.vaccine.2009.01.016","article-title":"Influenza virus CTL epitopes, remarkably conserved and remarkably variable","volume":"27","author":"Rimmelzwaan","year":"2009","journal-title":"Vaccine"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"1009","DOI":"10.1128\/JVI.02439-15","article-title":"Differential recognition of influenza A viruses by M1(58\u201366) epitope-specific CD8(+) T Cells is determined by extraepitopic amino acid residues","volume":"90","author":"Kreijtz","year":"2016","journal-title":"J. Virol."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"530","DOI":"10.1099\/vir.0.82120-0","article-title":"Assessment of the extent of variation in influenza A virus cytotoxic T-lymphocyte epitopes by using virus-specific CD8+ T-cell clones","volume":"88","author":"Berkhoff","year":"2007","journal-title":"J. Gen. Virol."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"1438","DOI":"10.3390\/v4091438","article-title":"Evasion of influenza A viruses from innate and adaptive immune responses","volume":"4","author":"Kreijtz","year":"2012","journal-title":"Viruses"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"21312","DOI":"10.1073\/pnas.0911915106","article-title":"Adaptive strategies of the influenza virus polymerase for replication in humans","volume":"106","author":"Mehle","year":"2009","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_60","doi-asserted-by":"crossref","unstructured":"Yamada, S., Hatta, M., Staker, B.L., Watanabe, S., Imai, M., Shinya, K., Sakaitagawa, Y., Ito, M., Ozawa, M., and Watanabe, T. (2010). Biological and structural characterization of a host-adapting amino acid in influenza virus. PLoS Path., 6.","DOI":"10.1371\/journal.ppat.1001034"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"1888","DOI":"10.1056\/NEJMoa1304459","article-title":"Human infection with a novel avian-origin influenza A (H7N9) virus","volume":"368","author":"Gao","year":"2013","journal-title":"N. Engl. J. Med."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"714","DOI":"10.1016\/S0140-6736(14)60111-2","article-title":"Clinical and epidemiological characteristics of a fatal case of avian influenza A H10N8 virus infection: A descriptive study","volume":"383","author":"Chen","year":"2014","journal-title":"Lancet."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"2352","DOI":"10.1038\/s41598-017-02598-z","article-title":"The PB2 mutation with lysine at 627 enhances the pathogenicity of avian influenza (H7N9) virus which belongs to a non-zoonotic lineage","volume":"7","author":"Li","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_64","doi-asserted-by":"crossref","unstructured":"Arai, Y., Kawashita, N., Daidoji, T., Ibrahim, M.S., Elgendy, E.M., Takagi, T., Takahashi, K., Suzuki, Y., Ikuta, K., and Nakaya, T. (2016). Novel polymerase gene mutations for human adaptation in clinical isolates of avian H5N1 influenza viruses. PLoS Path., 12.","DOI":"10.1371\/journal.ppat.1005583"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"210","DOI":"10.1016\/j.jfma.2017.02.011","article-title":"Human infection caused by an avian influenza A (H7N9) virus with a polybasic cleavage site in Taiwan, 2017","volume":"116","author":"Yang","year":"2017","journal-title":"J. Formos. Med. Assoc."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"558","DOI":"10.1128\/JVI.01785-09","article-title":"The effects of influenza A virus PB1-F2 protein on polymerase activity are strain specific and do not impact pathogenesis","volume":"84","author":"McAuley","year":"2010","journal-title":"J. Virol."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"2285","DOI":"10.1099\/vir.0.19302-0","article-title":"the origin of the 1918 pandemic influenza virus: A continuing enigma","volume":"84","author":"Reid","year":"2003","journal-title":"J. Gen. Virol."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"1015","DOI":"10.1038\/nrd2175","article-title":"Antiviral agents active against influenza A viruses","volume":"5","year":"2006","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_69","first-page":"1","article-title":"The NS segment of H5N1 avian influenza viruses (AIV) enhances the virulence of an H7N1 AIV in chickens","volume":"45","author":"Vergaraalert","year":"2014","journal-title":"Vet. Res."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1017\/S1466252307001272","article-title":"Up to new tricks\u2014A review of cross-species transmission of influenza A viruses","volume":"8","author":"Landolt","year":"2007","journal-title":"Anim. Health Res. Rev."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"2605","DOI":"10.1056\/NEJMoa0903810","article-title":"Emergence of a novel swine-origin influenza A (H1N1) virus in humans","volume":"360","author":"Dawood","year":"2009","journal-title":"N. Engl. J. Med."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1056\/NEJMp0904572","article-title":"Geographic dependence, surveillance, and origins of the 2009 influenza A (H1N1) virus","volume":"361","author":"Trifonov","year":"2009","journal-title":"N. Engl. J. Med."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"359","DOI":"10.3201\/eid2302.161252","article-title":"Novel reassortant clade 2.3.4.4 avian influenza A(H5N8) virus in wild aquatic birds, Russia, 2016","volume":"23","author":"Lee","year":"2017","journal-title":"Emerg. Infect. Dis."},{"key":"ref_74","doi-asserted-by":"crossref","unstructured":"Zhao, G., Gu, X., Lu, X., Pan, J., Duan, Z., Zhao, K., Gu, M., Liu, Q., He, L., and Chen, J. (2012). Novel reassortant highly pathogenic H5N2 avian influenza viruses in poultry in China. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0046183"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"1087","DOI":"10.3201\/eid2006.140233","article-title":"Novel reassortant influenza A(H5N8) viruses, South Korea, 2014","volume":"20","author":"Lee","year":"2014","journal-title":"Emerg. Infect. Dis."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"1368","DOI":"10.3201\/eid2308.170143","article-title":"Genesis of influenza A(H5N8) viruses","volume":"23","author":"Barman","year":"2017","journal-title":"Emerg. Infect. Dis."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"637","DOI":"10.3201\/eid2304.161866","article-title":"Highly pathogenic avian influenza A(H5N8) virus in wild migratory birds, Qinghai Lake, China","volume":"23","author":"Li","year":"2017","journal-title":"Emerg. Infect. Dis."},{"key":"ref_78","first-page":"111","article-title":"Outbreaks of avian influenza A (H5N2), (H5N8), and (H5N1) among birds\u2014United States, December 2014\u2013January 2015","volume":"64","author":"Jhung","year":"2015","journal-title":"MMWR Morb. Mortal. Wkly. Rep."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1186\/s13567-017-0435-4","article-title":"Infectivity, transmission and pathogenicity of H5 highly pathogenic avian influenza clade 2.3.4.4 (H5N8 and H5N2) United States index viruses in Pekin ducks and Chinese geese","volume":"48","author":"Bertran","year":"2017","journal-title":"Vet. Res."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"741","DOI":"10.3389\/fmicb.2017.00741","article-title":"Characterization of novel reassortant influenza A (H5N2) viruses isolated from poultry in Eastern China, 2015","volume":"8","author":"Wu","year":"2017","journal-title":"Front. Microbiol."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"462","DOI":"10.1006\/viro.1994.1555","article-title":"Nonhomologous recombination between the hemagglutinin gene and the nucleoprotein gene of an influenza virus","volume":"204","author":"Orlich","year":"1994","journal-title":"Virology"},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"693","DOI":"10.3201\/eid1004.030396","article-title":"Recombination resulting in virulence shift in avian influenza outbreak, Chile","volume":"10","author":"Suarez","year":"2004","journal-title":"Emerg. Infect. Dis."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"2691","DOI":"10.1099\/vir.0.19277-0","article-title":"Phylogenetic analysis reveals a low rate of homologous recombination in negative-sense RNA viruses","volume":"84","author":"Chare","year":"2003","journal-title":"J. Gen. Virol."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1016\/j.virol.2008.07.014","article-title":"Homologous recombination evidence in human and swine influenza A viruses","volume":"380","author":"He","year":"2008","journal-title":"Virology"},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"151","DOI":"10.3389\/fmicb.2013.00151","article-title":"Genetic variability and evolutionary dynamics of viruses of the family Closteroviridae","volume":"4","author":"Rubio","year":"2013","journal-title":"Front. Microbiol."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1016\/j.ijid.2016.01.002","article-title":"Is a highly pathogenic avian influenza virus H5N1 fragment recombined in PB1 the key for the epidemic of the novel AIV H7N9 in China, 2013?","volume":"43","author":"Chen","year":"2016","journal-title":"Int. J. Infect. Dis."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"1845","DOI":"10.1098\/rstb.2001.0998","article-title":"The haemagglutinin gene, but not the neuraminidase gene, of 'Spanish flu' was a recombinant","volume":"356","author":"Gibbs","year":"2001","journal-title":"Philos. Trans. R Soc. Lond. B Biol. Sci."},{"key":"ref_88","first-page":"359","article-title":"Evolution and ecology of influenza A viruses","volume":"385","author":"Yoon","year":"2014","journal-title":"Curr. Top. Microbiol. Immunol."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"187","DOI":"10.20506\/rst.28.1.1879","article-title":"Pandemic influenza\u2014Including a risk assessment of H5N1","volume":"28","author":"Taubenberger","year":"2009","journal-title":"Rev. Sci. Tech."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"615","DOI":"10.1038\/nature06945","article-title":"The genomic and epidemiological dynamics of human influenza A virus","volume":"453","author":"Rambaut","year":"2008","journal-title":"Nature"},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"43","DOI":"10.3810\/pgm.2009.09.2051","article-title":"The first pandemic of the 21st century: A review of the 2009 pandemic variant influenza A (H1N1) virus","volume":"121","author":"Scalera","year":"2009","journal-title":"Postgrad. Med."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"1916","DOI":"10.1016\/S0140-6736(13)60903-4","article-title":"Human infections with the emerging avian influenza A H7N9 virus from wet market poultry: Clinical analysis and characterisation of viral genome","volume":"381","author":"Chen","year":"2013","journal-title":"Lancet."},{"key":"ref_93","doi-asserted-by":"crossref","unstructured":"De Vries, R.P., Peng, W., Grant, O.C., Thompson, A.J., Zhu, X., Bouwman, K.M., de la Pena, A.T.T., van Breemen, M.J., Ambepitiya Wickramasinghe, I.N., and de Haan, C.A.M. (2017). Three mutations switch H7N9 influenza to human-type receptor specificity. PLoS Pathog., 13.","DOI":"10.1371\/journal.ppat.1006390"},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"243","DOI":"10.1126\/science.1242917","article-title":"Structures and receptor binding of hemagglutinins from human-infecting H7N9 influenza viruses","volume":"342","author":"Shi","year":"2013","journal-title":"Science"},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"102","DOI":"10.1038\/nature14348","article-title":"Dissemination, divergence and establishment of H7N9 influenza viruses in China","volume":"522","author":"Lam","year":"2015","journal-title":"Nature"},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"542","DOI":"10.3201\/eid2004.131295","article-title":"Active surveillance for avian influenza virus, Egypt, 2010-2012","volume":"20","author":"Kayali","year":"2014","journal-title":"Emerg. Infect. Dis."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"178","DOI":"10.1016\/j.ejphar.2017.05.038","article-title":"New drug-strategies to tackle viral-host interactions for the treatment of influenza virus infections","volume":"809","author":"Fischer","year":"2017","journal-title":"Eur. J. Pharmacol."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"1085","DOI":"10.1586\/14760584.2013.824709","article-title":"The evolving history of influenza viruses and influenza vaccines","volume":"12","author":"Hannoun","year":"2013","journal-title":"Expert Rev. Vaccines"},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"2036","DOI":"10.1056\/NEJMra1002842","article-title":"Influenza vaccines for the future","volume":"363","author":"Lambert","year":"2010","journal-title":"N. Engl. J. Med."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"7656","DOI":"10.1016\/j.vaccine.2007.08.042","article-title":"Safety and immunogenicity of a high dosage trivalent influenza vaccine among elderly subjects","volume":"25","author":"Couch","year":"2007","journal-title":"Vaccine"},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"121","DOI":"10.2147\/IDR.S105473","article-title":"Drug resistance in influenza A virus: The epidemiology and management","volume":"10","author":"Hussain","year":"2017","journal-title":"Infect. Drug Resist."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1111\/nyas.12462","article-title":"Continuing challenges in influenza","volume":"1323","author":"Webster","year":"2014","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1016\/j.antiviral.2016.01.012","article-title":"4th ISIRV antiviral group conference: Novel antiviral therapies for influenza and other respiratory viruses","volume":"129","author":"Fry","year":"2016","journal-title":"Antiviral. Res."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"23746","DOI":"10.1038\/srep23746","article-title":"Targeted disruption of influenza A virus hemagglutinin in genetically modified mice reduces viral replication and improves disease outcome","volume":"6","author":"Wang","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"26787","DOI":"10.1038\/srep26787","article-title":"Host genetics determine susceptibility to avian influenza infection and transmission dynamics","volume":"6","author":"Mwangi","year":"2016","journal-title":"Sci. Rep."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/18\/8\/1650\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T18:41:35Z","timestamp":1760208095000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/18\/8\/1650"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,8,7]]},"references-count":105,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2017,8]]}},"alternative-id":["ijms18081650"],"URL":"https:\/\/doi.org\/10.3390\/ijms18081650","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,8,7]]}}}